Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to 300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m 2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

The Current Molecular Epidemiological Scenario of Cryptosporidium, Giardia and Blastocystis in Spain. Implication for Public Health

The enteric protozoan parasites Cryptosporidium spp. and Giardia duodenalis are major contributors to the burden of gastrointestinal diseases globally. Both pathogens primarily affect children living in resource-poor settings with limited or no access to clean water and sanitation facilities, but are also significant public health threats in developed countries. Additionally, Cryptosporidium spp. and G. duodenalis are common causes of waterborne and foodborne outbreaks of gastrointestinal disease globally. Besides, the Stramenopile Blastocystis sp. is the most common eukaryotic organism reported in the human gut. Although its pathogenicity is a topic of debate, there is increasing evidence demonstrating that this protist can be associated with gastrointestinal disorders (diarrhoea, irritable bowel syndrome) and extra-intestinal manifestations, including urticaria. Because Cryptosporidium spp., G. duodenalis and Blastocystis sp. share the same transmission (faecal-oral) route, are able to infect a wide range of animal species other than humans with variable host specificities, and their infective forms are environmentally resilient, the study of these pathogens should be ideally approached under the One Health umbrella. In this context, molecular-based methods including PCR and sequencing provide powerful tools to investigate the epidemiology and transmission of these parasites. In Spain, cryptosporidiosis and giardiosis, but not blastocystosis, are notifiable diseases. However, the true incidence of these infections remain largely unknown because underdiagnosing and underreporting. Symptomatic cryptosporidiosis and giardiosis disproportionally affect children under four years of age, but we know now that subclinical infections are also common in apparently healthy individuals of all age groups. However, molecular data regarding the frequency and diversity of these pathogens are limited and spatially and temporally discontinuous. This chapter aims to provide, from a public veterinary health perspective, an updated account on the epidemiology of Cryptosporidium, G. duodenalis and Blastocystis in Spain, with an emphasis on the description of the species/genotypes circulating in symptomatic and asymptomatic human populations. Current knowledge on the presence of these pathogens in production (livestock), companion (dogs and cats) and wildlife animal species is also discussed, including their potential role as natural reservoirs of human infections, and the available evidence of zoonotic (and anthroponotic) transmission events.Research summarized in this chapter and conducted at the Spanish National Centre for Microbiology was funded by the Health Institute Carlos III (ISCIII), Ministry of Economy and Competitiveness (Spain), under projects CP12/03081 and PI16CIII/00024. The funder had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.S